Novel Imaging Techniques in Detection of Progressive Multiple Sclerosis

Abstract

Conventional brain imaging is increasingly used to support clinicians in diagnosing and monitoring the progression of multiple sclerosis (MS). Nevertheless, the correlation between a patient's clinical manifestation and conventional magnetic resonance imaging (MRI) measures is often weak, especially in patients with progressive MS (PMS). Imaging markers for monitoring disease progression in progressive multiple sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease evolution and to test effective treatments in clinical trials. Advanced imaging techniques that have the advantage of metrics with increased sensitivity to short-term tissue changes and increased specificity to the structural abnormalities characteristic of PMS have recently been applied in clinical trials of PMS. This study conducted on 200 Egyptian patients coming to MS clinic at Al-azhar university hospitals (120 female and 80 male) diagnosed as clinically definite multiple sclerosis according to 2017McDonald criteria for Multiple Sclerosis.The survey was conducted from May 2017 till May 2019. MS patients underwent baseline and 2-year follow-up scans. All patients underwent an examination by MS specialist neurologist including evaluation of the Expanded Disability Status Scale (EDSS) score and timed 25-foot walk (T25FW). All patients received disease-modifying immunotherapy during the observation period, as was selected and prescribed by their treating physician according to routine clinical care. The data came from the combination of computational tools of image processing and neuroimaging acquired in a 1.5 Tesla scanner using different techniques: Diffusion, T2,T1, FLAIR and Structural Morphometry. Data from more than 25 brain regions of 25 healthy individuals and 200 MS patients were collected. This study assessed MRI lesions from 200 clinically well-documented MS with a mean disease duration of 5 years, of whom 10 patients were diagnosed with primary progressive MS (PPMS), 15 with secondary progressive MS (SPMS), and175 with relapsing–remitting MS (RRMS). Twelve of them had an undetermined clinical course. We analysed the heterogeneity of lesion activity and its relationship to the disease course and severity. Compared with patients who had RRMS, those with progressive MS had a higher lesion load and a higher proportion of mixed active–inactive lesions, which helped to explain their greater disease severity (a shorter time to reach an EDSS score of 6). The study demonstrated that extensive cortical damage at disease onset and during the first 2 years of disease monitoring, as assessed by the number and volume of cortical lesions and cortical atrophy, was associated with a higher relapse rate during the study and more rapid onset of a progressive phase. Most importantly, a high cortical lesion count at disease onset predicted conversion to SPMS, and the number of lesions correlated with the speed of conversion (on average 4 years earlier in patients with ≥7 cortical lesions than in those with 1–3 lesions). None of the patients without cortical lesions at baseline evolved to SPMS. Combined with data from patients with clinically isolated syndrome, which suggest that cortical lesions are specific to MS and are associated with the accrual of more severe disability, these findings support the development of standardized MRI sequences for the assessment of cortical lesions in clinical practice. The importance of grey matter involvement for long-term prognosis was also confirmed by follow-up study of 49 patients with RRMS. An MRI model that included diffusion tensor measures of grey matter damage at baseline and measures of neurodegeneration — namely, formation of new T1-hypointense lesions and changes in brain volume — during the first 15 months of follow-up allowed the prediction of long-term disability in 77.6% of the patients. In contrast to previous studies of PPMS with a shorter follow-up (2 years), spinal cord atrophy was not associated with clinical deterioration, suggesting that the processes leading to accrual of disability evolve over time. Conventional and modern magnetic-resonance-based techniques to the study of MS has improved our ability to diagnose and monitor MS, as well as our understanding of disease pathophysiology. New techniques need to be refined and validated before they can be properly integrated into clinical research and practice. New schemes and analysis procedures require standardisation and optimisation so that they can be used in multi-site settings, both in natural history studies and treatment trials. From the data available, it is evident that the combining of different magnetic resonance methods, which are sensitive to different aspects of MS pathology, is a promising way to increase further our understanding of the mechanisms underlying the accumulation of irreversible disability.